Various approaches have been aimed at the treatment of diseases caused or manifested by enhanced secretion of an otherwise normal protein, production of a pathological soluble or membrane bound protein, or abnormal conformational changes or folding of a peptide or protein in a mammal. Traditional techniques to target such toxic proteins or the aberrant expression of proteins include the administration of small molecules to affect the rate or amount of production of the proteins or antibodies that will specifically bind to proteins of interest and cause them to be cleared from the body.
The administration of therapeutic antibodies or antibody fragments has had drawbacks that limit their applicability in humans, particularly when administered into the blood stream. New techniques such as chimerization and humanization have been developed to reduce the immunogenicity of the antibodies or antibody fragments. Some newly developed antibodies are completely free of epitopes recognized as foreign by the human immune system and may be generated by using transgenic mouse systems or phage/phagemid display. Such completely humanized antibodies are the driving force behind the fast-paced expansion of antibody product pipelines. Problems, such as toxicity, short-half life, and inability of antibody to cross the blood-brain-barrier (BBB), still exist.
Methods and agents that will enhance the neutralization or clearance of certain proteins in the brain and delivery devices to aid in the administration of such agents is desired.